Feline alimentary lymphoma

What it is

Lymphoma is the most common tumour of the cat, and the alimentary (gastrointestinal) form is now its most frequent presentation. Neoplastic lymphocytes infiltrate the wall of the stomach, small intestine or, less often, the large intestine, together with the mesenteric lymph nodes and sometimes the liver. Several forms with very different behaviour are recognised:

• Low-grade (small cell) lymphoma: almost always of T lymphocytes, with diffuse infiltration of the small intestinal mucosa, especially the jejunum and ileum. It progresses over months to years and is hard to distinguish from chronic inflammatory bowel disease, from which it may arise in some cases.
• Intermediate- or high-grade (large cell) lymphoma: of B or T lymphocytes; it forms transmural masses that can obstruct or perforate the intestine. It progresses over weeks.
• Large granular lymphocyte lymphoma: an aggressive T- or NK-cell variant that often affects the jejunum and mesenteric lymph nodes.

In the past many feline lymphomas were associated with feline leukaemia virus (FeLV); today, with vaccination and control of the virus, most cats with alimentary lymphoma are FeLV-negative. Exposure to tobacco smoke has been linked to lymphoma risk.

Who it affects

Older cats, usually over 10 years in the low-grade form. High-grade forms occur over a wider age range.

Anatomy involved

• Small intestine: in low-grade lymphoma, diffusely thickened wall, often with a thickened muscularis propria; in high-grade lymphoma, masses that efface the wall layers.
• Mesenteric lymph nodes: enlarged, sometimes forming a palpable abdominal mass.
• Stomach, ileocaecocolic junction, liver and spleen: other locations.

Clinical signs

Chronic weight loss, vomiting, diarrhoea (small-bowel type), reduced or occasionally increased appetite. In the low-grade form signs are slow and resemble those of an inflammatory enteropathy. In high-grade forms: anorexia, lethargy, a palpable abdominal mass and signs of obstruction or of peritonitis from perforation.

Diagnosis

• Abdominal palpation: thickened bowel loops or masses, enlarged mesenteric lymph nodes.
• Blood work: often hypocobalaminaemia (low vitamin B12), hypoalbuminaemia; T4 and kidney function are assessed in older cats.
• Abdominal ultrasound: wall thickening, loss of layering in masses, muscularis thickening and enlarged lymph nodes; it guides sampling.
• Aspiration cytology: usually enough for large cell lymphoma.
• Endoscopic or full-thickness surgical biopsies for low-grade disease, with immunohistochemistry (B or T immunophenotype) and clonality testing (PARR). According to the 2023 ACVIM consensus, distinguishing low-grade lymphoma from inflammatory enteropathy requires integrating histology, immunophenotype and clonality, and is sometimes not possible with certainty. Duodenal biopsies alone may miss jejunal and ileal lesions.

Treatment

• Low grade: oral prednisolone and chlorambucil, together with cobalamin supplementation and a highly digestible diet. Most cats respond and many live with a good quality of life for years.
• Intermediate or high grade: multi-agent chemotherapy (COP- or CHOP-type protocols, with cyclophosphamide, vincristine, doxorubicin and prednisolone); surgery for obstruction or perforation. Response is more variable and survival is usually measured in months, although cats that achieve complete remission may live much longer.
• Large granular lymphocyte lymphoma: poor prognosis.

Key studies

Low-grade lymphoma or inflammatory enteropathy?

• ACVIM consensus (Marsilio et al., 2023): no single criterion or biomarker reliably separates lymphoplasmacytic enteritis from low-grade intestinal T-cell lymphoma. The diagnosis integrates all clinical and diagnostic data, with histopathology as the mainstay, and most recommendations rest on moderate or low-level evidence.
• Freiche et al. (2021), prospective cohort of 44 cats (22 with low-grade lymphoma, 22 with lymphoplasmacytic enteritis). A monomorphic lymphocyte population (22 of 22), deep mucosal infiltration (68%) and epithelial nests or plaques (50% versus 5%) pointed to lymphoma. Clonality testing found monoclonality in 86% of the lymphomas, but also in 70% of the cats with enteritis (40% monoclonal, 30% monoclonal on a polyclonal background), so a clonal result does not prove lymphoma on its own.
• Evans et al. (2006), prospective study of 22 cats sampled by endoscopy and then by full-thickness surgical biopsy. All 10 cats with lymphoma had it in the jejunum and ileum, and 9 in the duodenum. Endoscopic biopsies confirmed it in 3, were inconclusive in 3 and led to a wrong diagnosis of inflammatory bowel disease in 4.
• Scott et al. (2011), retrospective study of 70 cats with endoscopic biopsies of both the duodenum and the ileum. Of the 18 with small cell lymphoma, 39% had it only in the duodenum and 44% only in the ileum, and agreement between the two sites was poor (kappa 0.23). A single pathologist reviewed the samples.

Treatment and outcome

• Kiselow et al. (2008), retrospective series of 41 cats with low-grade lymphoma, confined to the gastrointestinal tract in 68%, treated with prednisone and chlorambucil. 56% achieved a complete response and 39% a partial response, and median survival was 704 days. 78% of the cats tested had low cobalamin.
• Bernardo Marques et al. (2024), multicentre retrospective study of 57 cats with high-grade or large granular lymphocyte alimentary lymphoma treated with COP- or CHOP-based protocols. Complete response was 20%, overall response 42% and median survival 131 days. Diffuse infiltration of the gastrointestinal tract and involvement of a non-haematopoietic organ were negative prognostic factors.